Infants in the Neonatal Intensive Care Unit (NICU) are exposed to stressful stimuli such as loud noises, bright lights, blood drawing, suctioning and intubation, and are frequently left in isolates with minimal proper interaction. Stress has been demonstrated to exert a negative effect on the immune system in general, and on Natural Killer (NK) cells (the population of large granular lymphocytes with cytotoxic activity against tumor cells or virus-infected cells) in particular. Different psychological interventions including relaxation have been used in efforts to reduce stress, and several of these techniques have been shown to improve cellular immunity and to enhance NK cell number and function. Massage therapy (MT) has been used to reduce stress in premature infants and has been associated with weight gain, shorter hospital stay, and improvement in mental/motor development. While MT has been shown to increase the number and function of NK cells in healthy adults and in adults infected with HIV, the effect of MT on the immune system of children including premature infants has never been investigated. We hypothesize that in premature infants, MT will enhance the immune system in general, and the number and function of NK cells in particular, and will result in reduced stress cortisol levels in addition to weight gain and shorter hospital stay. Ninety-six stable premature infants meeting selection criteria will be randomized to massage and sham treatment groups. Study intervention (massage and sham) will be given 45 min/day, 5 days/week for 4 weeks behind two screens. Immunologic evaluation (blood count, total T cells/subsets, B cells, NK cells numbers/functions) and salivary cortisol analysis will be performed on both groups at baseline, 2 weeks, and at end of therapy. Physicians, nurses, parents, will be masked. Daily weights, number of infections, amount of feeding and days in the hospital will be recorded. Data will be analyzed using the SPSS software version 12.0. Our unique and innovative study will be the largest study in this area and will provide valuable information on potential immune parameters associated with stress reduction and improved development in premature infants undergoing massage therapy. Data from this study could also impact future explorations on potential effects of MT on the immune responses to childhood vaccinations and susceptibility to bacterial and viral infections. [unreadable] [unreadable]